RESUMEN
BACKGROUND: Type 1 diabetes (T1D) is a complex disease, with involvement of various susceptibility genes. Human leukocyte antigen (HLA) on chromosome 6p21 is major susceptibility region. This study examined genetic association of HLA genes with T1D. METHODS: The study recruited 259 T1D patients and 706 controls from north India. PCR-SSP and LiPA were used to type HLA Class I and II alleles. RESULTS: At HLA Class I locus, HLA-A*02, A*26, B*08 and B*50 were significantly increased in patients vs controls (39.8% vs 28.9% [Bonferroni-corrected P {Pc } = 0.032], 24.7% vs 9.6% [Pc = 4.83 × 10-8 ], 37.2% vs 15.7% [Pc = 1.92 × 10-9 ], and 19.4% vs 5.5% [Pc = 4.62 × 10-9 ], respectively). Similarly, in Class II region, DRB1*03 showed a strong positive association with T1D (78.7% vs 17.5% in controls; P = 1.02 × 10-9 ). Association of DRB1*04 with T1D (28.3% vs 15.5% in controls; Pc = 3.86 × 10-4 ) was not independent of DRB1*03. Negative associations were found between T1D and DRB1*07, *11, *13, and *15 (13.8% vs 26.1% in controls [Pc = 0.00175], 3.9% vs 16.9% in controls [Pc = 6.55× 10-6 ], 5.5% vs 21.6% in controls [Pc = 2.51 × 10-7 ], and 16.9% vs 43.9% in controls [Pc = 9.94× 10-10 ], respectively). Compared with controls, patients had significantly higher haplotype frequencies of A*26-B*08-DRB1*03-DQA1*05-DQB1*02 (10.43% vs 1.96%; P = 7.62 × 10-11 ), A*02-B*50-DRB1*03-DQA1*05-DQB1*02 (6.1% vs 0.71%; P = 2.19 × 10-10 ), A*24-B*08-DRB1*03-DQA1*05-DQB1*02 (4.72% vs 0.8%; P = 5.4 × 10-7 ), A*02-B*08-DRB1*03-DQA1*05-DQB1*02 (2.36% vs 0.18%; P = 3.6 × 10-5 ), and A*33-B*58-DRB1*03-DQA1*05-DQB1*02 (4.33% vs 1.25%; P = 0.00019). CONCLUSIONS: In north India, T1D is independently associated only with HLA-DRB1*03 haplotypes, and is negatively associated with DRB1*07, *11, *13, and *15.